LUISA LINA VILLA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina - Docente
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
20 resultados
Resultados de Busca
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conferenceObject Co-infection with Epstein-Barr virus impacts oral HPV persistence(2022) DICKEY, Brittney L.; GIULIANO, Anna R.; SIRAK, Bradley; ABRAHAMSEN, Martha; LAZCANO-PONCE, Eduardo; VILLA, Luisa L.; COGHILL, Anna E.- TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line(2022) MORALE, Mirian Galliote; TAMURA, Rodrigo Esaki; CINTRA, Ricardo; ARAUJO, Natalia Meneses; VILLA, Luisa LinaHuman Papillomavirus is responsible for a wide range of mucosal lesions and tumors. The immune system participate in tumorigenesis in different ways. For example, signaling pathways triggered by Toll-like receptors (TLR) play a role in chemotherapy resistance in several tumor types and are candidates for contributing to the development of HPV-induced tumors. Here, we studied the receptor TLR4 and the adaptor molecule SARM1 in HeLa cells, an HPV-positive cervical cancer cell line. Knocking out of these genes individually proved to be important for maintaining cell viability and proliferation. TLR4 knock out cells were more sensitive to cisplatin treatment, which was illustrated by an increased frequency of apoptotic cells. Furthermore, TLR4 and SARM1 modulated ROS production, which was induced by cell death in response to cisplatin. In conclusion, TLR4 and SARM1 are important for therapy resistance and cervical cancer cell viability and may be relevant clinical targets.
- The Association between Smoking and Anal Human Papillomavirus in the HPV Infection in Men Study(2022) UMUTONI, Victoria; SCHABATH, Matthew B.; NYITRAY, Alan G.; WILKIN, Timothy J.; VILLA, Luisa L.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.; SUDENGA, Staci L.Background: Previous studies show an association between smoking and anal cancer. The objective of this study was to assess the association between smoking and anal HPV (human papillo-mavirus) prevalence, incidence, and persistence in men. Methods: The HPV Infection in Men (HIM) Study is a multinational study that enrolled HIV-negative men. At baseline and follow-up visits, anal specimens were collected. HPV geno-typing was assessed by linear array. Prevalence ratios (PR) were used to assess the association between smoking and anal HPV prevalence. Odds ratios (OR) were used to assess the association between smoking and anal HPV incidence and >= 12-months persistence. Results: Current smokers have a higher prevalence [adjusted PR (aPR), 1.36; 95% confidence interval (CI), 1.06-1.73) and incidence [adjusted OR (aOR), 1.74; 95% CI, 1.26-2.39] and >= 12-months persistence (aOR, 1.67; 95% CI, 1.19-2.33) of any anal HPV compared with never smokers. There were no differences in the prevalence, incidence, or persistence of anal HPV between former and never smokers. Smoking status was not associated with the prevalence or persistence of anal HPV among men who have sex with men but was associated with higher incidence of HR-HPV. Among men that have sex with women (MSW), current smokers had an increased prevalence and incidence of LR-HPV compared with never smokers. Conclusions: Current smokers had a higher prevalence, persistence, and incidence of HPV compared with never smokers. Further research is needed to assess the role smoking in anal HPV persis-tence and progression to disease. Impact: Prevention initiatives should raise awareness about smoking and the risk factor of anal HPV infection and anal cancer.
conferenceObject Logistical issues in implementing a clinical trial on oral cancer prevention through HPV vaccination: Implementation of Ulacnet201 in Mexico(2022) ALLEN-LEIGH, Betania; PORTILLO-ROMERO, Alejandra; QUITERIO, Manuel; ACOSTA, Maribel; RIVERA-RAMIREZ, Abraham; SANCHEZ, Guillermina; CRUZ, Aurelio; BARRIENTOS, Tonatiuh; MAGIS, Carlos; ISAACS-SORIANO, Kimberly; ABRAHAMSEN, Martha E.; HOUSE, Margaret; BROFSKY, Emma; SAHASRABUDDHE, Vikrant; WILKIN, Timothy; GIULIANO, Anna; VILLA, Luisa; LAZCANO-PONCE, Eduardo- A positive HPV test with positive p16/Ki-67 double staining in self-sampled vaginal material is an accurate tool to detect women at risk for cervical cancer(2022) LORENZI, Noely P. C.; TERMINI, Lara; FERREIRA-FILHO, Edson S.; NUNES, Rafaella A. L.; SILVA, Gabriela A. F.; LEPIQUE, Ana P.; LONGATTO-FILHO, Adhemar; TACLA, Maricy; BARACAT, Edmund C.; VILLA, Luisa L.; SOARES-JUNIOR, Jose M.BACKGROUND: The development of efficient strategies for managing high-risk human papillomavirus (HR-HPV)-positive women is a major challenge when human papillomavirus-based primary screening is being performed. The objectives of this study were to evaluate the comparative effectiveness of HR-HPV testing based on self-collection (SC) and HR-HPV testing based on collection by a health professional (HP) and to assess the potential usefulness of HR-HPV testing combined with testing with the biomarkers p16/Ki-67, alpha-mannosidase, and superoxide dismutase 2 (SOD2). METHODS: This was a cross-sectional study of 232 women admitted for colposcopy because of an abnormal Papanicolaou smear. The collected material underwent liquid-based cytology, HR-HPV detection, and immunocytochemical testing (p16/Ki-67, alpha-mannosidase, and SOD2). The gold standard was the histopathological result; the positive reference was CIN2+. RESULTS: The overall accuracy of HR-HPV testing was 76.6%; the results for the SC group (78.1%) and the HP group (75.2%) were similar. The positive predictive values (HP, 76.5%; SC, 80.0%), the negative predictive values (HP, 66.7%; SC, 64.3%), the positive likelihood values (HP, 1.35; SC, 1.36), and the negative likelihood values (HP, 0.21; SC, 0.19) were also similar. p16/Ki-67 showed higher sensitivity than the other 2 biomarkers: 78.1% versus 45.8% for alpha-mannosidase and 44.5% for SOD2. The specificities of the biomarkers were equivalent: 71.4% for p16/Ki-67, 77.8% for alpha-mannosidase, and 71.2% for SOD2. In the HP group, accuracy also leaned more heavily toward the final score (using alpha-mannosidase and SOD2) without statistical significance (80.8% vs 77.9%). The contrast with the SC group yielded the same level of accuracy. CONCLUSIONS: SC, when associated with testing with biomarkers, is as accurate as collection by HPs in the detection of women at risk for cervical cancer.
- Is there a higher frequency of anal dysplasia and infection by human papillomavirus in Crohn?s disease patients?(2022) GUZELA, V. R.; SOBRADO JR., C. W.; NADAL, S. R.; VILLA, L. L.; MOTA, G. R.; GONCALVES, A. P.; NADAL, C. R. M.; NAHAS, C. S. R.; NAHAS, S. C.The aim of this study was to compare the frequency of dysplasia and human papillomavirus (HPV) infection in the anal canal of patients with Crohn???s disease (CD) with a control group and assess whether there is a correlation between use of immunosuppressants and anal manifestation of CD. Patients with CD and control individuals were submitted to anal cytology and material collection for polymerase chain reaction (PCR). The cytology was classified as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade (HSIL). PCR was considered positive or negative according to virus presence or absence. A total of 117 patients were included (54 in the control group and 63 in the CD group, being 32 without and 31 with immunosuppressants). ASCUS and LSIL were found in 25.9 and 22.2% of control patients and 28.6 and 39.7% of CD patients. HPV was identified in 14.8% of the control group and 27% of the CD group. In CD patients, HPV was found in 37.5 and 16.1% of those without and with immunosuppressants, respectively. Patients with perianal involvement had 15.6% of PCR positivity. There was no statistical difference in dysplasia and infection by HPV between the groups. Use of immunosuppressants did not influence the result, but anal manifestation was inversely proportional to viral detection.
conferenceObject Logistical issues in implementing a clinical trial on oral cancer prevention through HPV vaccination: Implementation of Ulacnet201 in Mexico.(2022) ALLEN-LEIGH, Betania; PORTILLO-ROMERO, Alejandra; QUITERIO, Manuel; ACOSTA, Maribel; RIVERA-RAMIREZ, Abraham; SANCHEZ, Guillermina; CRUZ, Aurelio; BARRIENTOS, Tonatiuh; MAGIS, Carlos; ISAACS-SORIANO, Kimberly; ABRAHAMSEN, Martha E.; HOUSE, Margaret; BROFSKY, Emma; SAHASRABUDDHE, Vikrant; WILKIN, Timothy; GIULIANO, Anna; VILLA, Luisa; LAZCANO-PONCE, Eduardo- Vaginal Microbiome Components as Correlates of Cervical Human Papillomavirus Infection(2022) MORALES, Julia Andrade Pessoa; MARCONI, Camila; EL-ZEIN, Mariam; RAVEL, Jacques; PINTO, Gabriel Victor da Silva; SILVEIRA, Rosana; LIMA, Moises Diogo de; CARVALHO, Newton Sergio de; ALVES, Rosane Ribeiro Figueiredo; PARADA, Cristina Maria Garcia de Lima; LEITE, Sandra Helena Morais; VILLA, Luisa L.; FRANCO, Eduardo L.; SILVA, Marcia Guimaraes daBackground Interplay between vaginal microbiome and human papillomavirus (HPV) remains unclear, partly due to heterogeneity of microbiota. Methods We used data from 546 women enrolled in a cross-sectional study in 5 Brazil. We genotyped vaginal samples for HPV and sequenced V3-V4 region of 16S rRNA gene for vaginal microbiome analysis. We used stepwise logistic regression to construct 2 linear scores to predict high-risk HPV (hrHPV) positivity: one based exclusively on presence of individual bacterial taxa (microbiome-based [MB] score) and the other exclusively on participants' sociodemographic, behavioral, and clinical (SBC) characteristics. MB score combined coefficients of 30 (of 116) species. SBC score retained 6 of 25 candidate variables. We constructed receiver operating characteristic curves for scores as hrHPV correlates and compared areas under the curve (AUC) and 95% confidence intervals (CI). Results Overall, prevalence of hrHPV was 15.8%, and 26.2% had a Lactobacillus-depleted microbiome. AUCs were 0.8022 (95% CI, .7517-.8527) for MB score and 0.7027 (95% CI, .6419-.7636) for SBC score (P = .0163). Conclusions The proposed MB score is strongly correlated with hrHPV positivity-exceeding the predictive value of behavioral variables-suggesting its potential as an indicator of infection and possible value for clinical risk stratification. This cross-sectional study demonstrated a strong correlation between vaginal microbiome components and cervical high-risk HPV positivity.
- Biomarkers of human papillomavirus (HPV)-driven head and neck cancer in Latin America and Europe study: Study design and HPV DNA/p16(INK4a) status(2022) SICHERO, Laura; TAGLIABUE, Marta; MOTA, Giana; FERREIRA, Silvaneide; NUNES, Rafaella A. L.; CASTANEDA, Carlos Arturo; CASTILLO, Miluska; CORREA, Rita Mariel; PERDOMO, Sandra; RODRIGUEZ-URREGO, Paula A.; MATOS, Leandro Luongo; MOHSSEN, Ansarin; GHEIT, Tarik; TOMMASINO, Massimo; CHIOCCA, Susanna; VILLA, Luisa LinaBackground Human papillomavirus (HPV)-driven head/neck squamous cell carcinomas (HNSCC) prevalence varies globally. We evaluated HPV DNA and p16(INK4a) in formalin fixed paraffin embedded (FFPE) HNSCC from Argentina, Brazil, Colombia, and Peru. Methods HPV was genotyped by PCR-hybridization. All HPV DNA positive and some HPV DNA negative cases underwent p16(INK4a) immunohistochemistry. Results HPV DNA was detected in 32.8%, 11.1%, and 17.8% of oropharyngeal (OPC), oral cavity (OCC) and laryngeal (LC) cancers, respectively. OPC HPV prevalence was higher in Colombia (94.7%), and Argentina (42.6%) compared to Brazil (10.6%) and Peru (0.0%). HPV-16 was the most detected. Other HPVs were found in LC. Higher rates of p16(INK4a) positivity were observed among HPV positive OPC/OCC cases compared to LC cases. Conclusions Our results support a role for HPV-16 in a subset of HNSCC, corroborate the heterogeneity observed in samples from different countries, and contribute additional etiological and biomarkers information in tumors of significant impact worldwide.
- Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma(2022) MUNARI, F. F.; SICHERO, L.; CARLONI, A. C.; LACERDA, C. F.; NUNES, E. M.; OLIVEIRA, A. T. T. De; SCAPULATEMPO-NETO, C.; SILVA, S. R. M. Da; CREMA, E.; ADAD, S. J.; RODRIGUES, M. A. M.; HENRY, M. A. C. A.; GUIMARãES, D. P.; REIS, R. M.; VILLA, L. L.; LONGATTO-FILHO, A.Background: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC). Objective: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals. Methods: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology. Results: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics. Conclusion: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.